Genome-wide association study in 8,956 German individuals identifies influence of ABO histo-blood groups on gut microbiome.

Malte Christoph Rühlemann, Britt Marie Hermes, Corinna Bang, Shauni Doms, Lucas Moitinho-Silva, Louise Bruun Thingholm, Fabian Frost, Frauke Degenhardt, Michael Wittig, Jan Kässens, Frank Ulrich Weiss, Annette Peters, Klaus Neuhaus, Uwe Völker, Henry Völzke, Georg Homuth, Stefan Weiss, Harald Grallert, Matthias Laudes, Wolfgang Lieb, Dirk Haller, Markus M Lerch, John F Baines, Andre Franke

Journal: Nature genetics 2021;53(2):147-155

PMID: 33462482

Full Text on Nature Publishing Group View on PubMed

Abstract

The intestinal microbiome is implicated as an important modulating factor in multiple inflammatory, neurologic and neoplastic diseases. Recent genome-wide association studies yielded inconsistent, underpowered and rarely replicated results such that the role of human host genetics as a contributing factor to microbiome assembly and structure remains uncertain. Nevertheless, twin studies clearly suggest host genetics as a driver of microbiome composition. In a genome-wide association analysis of 8,956 German individuals, we identified 38 genetic loci to be associated with single bacteria and overall microbiome composition. Further analyses confirm the identified associations of ABO histo-blood groups and FUT2 secretor status with Bacteroides and Faecalibacterium spp. Mendelian randomization analysis suggests causative and protective effects of gut microbes, with clade-specific effects on inflammatory bowel disease. This holistic investigative approach of the host, its genetics and its associated microbial communities as a 'metaorganism' broaden our understanding of disease etiology, and emphasize the potential for implementing microbiota in disease treatment and management.

Address: Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.; Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Plön, Germany.; Institute of Experimental Medicine, Kiel University, Kiel, Germany.; Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.; Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Plön, Germany.; Institute of Experimental Medicine, Kiel University, Kiel, Germany.; Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.; Department of Dermatology, Kiel University, Kiel, Germany.; Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.; German Center for Diabetes Research, Neuherberg, Germany.; ZIEL-Institute for Food & Health, Technical University of Munich, Freising, Germany.; Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.; Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.; Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.; Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany.; Department of Internal Medicine 1, Kiel University, Kiel, Germany.; Institute of Epidemiology, Kiel University, Kiel, Germany.; ZIEL-Institute for Food & Health, Technical University of Munich, Freising, Germany.; Chair of Nutrition and Immunology, Technical University of Munich, Freising, Germany.; Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany. [email protected].

DOI: 10.1038/s41588-020-00747-1

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MeSH Terms: ABO Blood-Group System, Bacteroides, Faecalibacterium, Fucosyltransferases, Gastrointestinal Microbiome, Genome-Wide Association Study, Germany, Humans, Lactase, Linkage Disequilibrium, Mendelian Randomization Analysis, Galactoside 2-alpha-L-fucosyltransferase